St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital, University of New South Wales, Sydney, Australia.
Nephrol Dial Transplant. 2012 Jan;27(1):70-5. doi: 10.1093/ndt/gfr575. Epub 2011 Sep 22.
Elevated macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels in serum mediate anorexia and weight loss in some cancer patients and similarly elevated levels occur in chronic kidney disease (CKD). Serum MIC-1/GDF15 is also elevated in chronic inflammatory diseases and predicts atherosclerotic events independently of traditional risk factors. The relationship between chronic inflammation, decreasing body mass index (BMI) and increased mortality in CKD is not well understood and is being actively investigated. MIC-1/GDF15 may link these features of CKD.
Cohorts of incident dialysis patients from Sweden (n = 98) and prevalent hemodialysis patients from the USA (n = 381) had serum MIC-1/GDF15, C-reactive protein (CRP) levels and BMI measured at study entry. Additional surrogate markers of nutritional adequacy, body composition and inflammation were assessed in Swedish patients. Patients were followed for all-cause mortality.
In the Swedish cohort, serum MIC-1/GDF15 was associated with decreasing BMI, measures of nutrition and markers of oxidative stress and inflammation. Additionally, high serum MIC-1/GDF15 levels identified patients with evidence of protein-energy wasting who died in the first 3 years of dialysis. The ability of serum MIC-1/GDF15 to predict mortality in the first 3 years of dialysis was confirmed in the USA cohort. In both cohorts, serum MIC-1/GDF15 level was an independent marker of mortality when adjusted for age, CRP, BMI, history of diabetes mellitus and/or cardiovascular disease and glomerular filtration rate or length of time on dialysis at study entry.
MIC-1/GDF15 is a novel independent serum marker of mortality in CKD capable of significantly improving the mortality prediction of other established markers. MIC-1/GDF15 may mediate protein-energy wasting in CKD and represent a novel therapeutic target for this fatal complication.
血清中巨噬细胞抑制细胞因子-1（MIC-1/GDF15）水平升高可介导部分癌症患者出现厌食和体重减轻，类似地，慢性肾脏病（CKD）患者也会出现 MIC-1/GDF15 水平升高。血清 MIC-1/GDF15 在慢性炎症性疾病中也升高，并可独立于传统危险因素预测动脉粥样硬化事件。慢性炎症、体重指数（BMI）下降和 CKD 患者死亡率增加之间的关系尚未得到很好的理解，目前正在积极研究。MIC-1/GDF15 可能将 CKD 的这些特征联系起来。
来自瑞典的初发透析患者队列（n = 98）和来自美国的现患血液透析患者队列（n = 381）在研究入组时测量了血清 MIC-1/GDF15、C 反应蛋白（CRP）水平和 BMI。在瑞典患者中还评估了营养充足、身体成分和炎症的替代标志物。对患者进行全因死亡率随访。
在瑞典队列中，血清 MIC-1/GDF15 与 BMI 下降、营养指标以及氧化应激和炎症标志物有关。此外，高血清 MIC-1/GDF15 水平可识别出在透析的前 3 年内出现蛋白能量消耗且死亡的患者。在美国队列中也证实了血清 MIC-1/GDF15 预测透析前 3 年死亡率的能力。在两个队列中，血清 MIC-1/GDF15 水平在调整年龄、CRP、BMI、糖尿病和/或心血管疾病病史以及肾小球滤过率或研究入组时透析时间后，是死亡率的独立标志物。
MIC-1/GDF15 是 CKD 死亡率的一种新的独立血清标志物，可显著提高其他已确立标志物的死亡率预测能力。MIC-1/GDF15 可能介导 CKD 中的蛋白能量消耗，并代表这种致命并发症的一种新的治疗靶点。
